Wounding of Arabidopsis halleri leaves enhances cadmium accumulation that acts as a defense against herbivory.

Approximately 0.2 % of all angiosperms are classified as metal hyperaccumulators based on their extraordinarily high leaf metal contents, for example >1 % zinc, >0.1 % nickel or >0.01 % cadmium (Cd) in dry biomass. So far, metal hyperaccumulation has been considered to be a taxon-wide, constitutively expressed trait, the extent of which depends solely on available metal concentrations in the soil. Here we show that in the facultative metallophyte Arabidopsis halleri, both insect herbivory and mechanical wounding of leaves trigger an increase specifically in leaf Cd accumulation. Moreover, the Cd concentrations accumulated in leaves can serve as an elemental defense against herbivory by larvae of the Brassicaceae specialist small white (Pieris rapae), thus allowing the plant to take advantage of this non-essential trace element and toxin. Metal homeostasis genes are overrepresented in the systemic transcriptional response of roots to the wounding of leaves in A. halleri, supporting that leaf Cd accumulation is preceded by systemic signaling events. A similar, but quantitatively less pronounced transcriptional response was observed in A. thaliana, suggesting that the systemically regulated modulation of metal homeostasis in response to leaf wounding also occurs in non-hyperaccumulator plants. This is the first report of an environmental stimulus influencing metal hyperaccumulation.

Ash2 acts as an Ecdysone Receptor coactivator by stabilizing the histone methyltransferase Trr.

The molting hormone ecdysone triggers chromatin changes via histone modifica- tions that are important for gene regulation. On hormone activation, the ecdysone receptor (EcR) binds to the SET domain-containing histone H3 methyltransferase trithorax-related protein (Trr). Methylation of histone H3 at lysine 4 (H3K4me), which is associated with tran- scriptional activation, requires several cofactors, including Ash2. We find that ash2 mutants have severe defects in pupariation and metamorphosis due to a lack of activation of ecdy- sone-responsive genes. This transcriptional defect is caused by the absence of the H3K4me3 marks set by Trr in these genes. We present evidence that Ash2 interacts with Trr and is re- quired for its stabilization. Thus we propose that Ash2 functions together with Trr as an ecdysone receptor coactivator.

Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data.

BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). METHODS: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. RESULTS: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). CONCLUSIONS: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.

Nuclear Factor I-C acts as a regulator of hepatocyte proliferation at the onset of liver regeneration.

BACKGROUND & AIMS: Knockout studies of the murine Nuclear Factor I-C (NFI-C) transcription factor revealed abnormal skin wound healing and growth of its appendages, suggesting a role in controlling cell proliferation in adult regenerative processes. Liver regeneration following partial hepatectomy (PH) is a well-established regenerative model whereby changes elicited in hepatocytes lead to their rapid and phased proliferation. Although NFI-C is highly expressed in the liver, no hepatic function was yet established for this transcription factor. This study aimed to determine whether NFI-C may play a role in hepatocyte proliferation and liver regeneration. METHODS: Liver regeneration and cell proliferation pathways following two-thirds PH were investigated in NFI-C knockout (ko) and wild-type (wt) mice. RESULTS: We show that the absence of NFI-C impaired hepatocyte proliferation because of plasminogen activator I (PAI-1) overexpression and the subsequent suppression of urokinase plasminogen activator (uPA) activity and hepatocyte growth factor (HGF) signalling, a potent hepatocyte mitogen. This indicated that NFI-C first acts to promote hepatocyte proliferation at the onset of liver regeneration in wt mice. The subsequent transient down regulation of NFI-C, as can be explained by a self-regulatory feedback loop with transforming growth factor beta 1 (TGF-ß1), may limit the number of hepatocytes entering the first wave of cell division and/or prevent late initiations of mitosis. CONCLUSION: NFI-C acts as a regulator of the phased hepatocyte proliferation during liver regeneration.

The Drosophila TNF Eiger Is an Adipokine that Acts on Insulin-Producing Cells to Mediate Nutrient Response.

Adaptation of organisms to ever-changing nutritional environments relies on sensor tissues and systemic signals. Identification of these signals would help understand the physiological crosstalk between organs contributing to growth and metabolic homeostasis. Here we show that Eiger, the Drosophila TNF-α, is a metabolic hormone that mediates nutrient response by remotely acting on insulin-producing cells (IPCs). In the condition of nutrient shortage, a metalloprotease of the TNF-α converting enzyme (TACE) family is active in fat body (adipose-like) cells, allowing the cleavage and release of adipose Eiger in the hemolymph. In the brain IPCs, Eiger activates its receptor Grindelwald, leading to JNK-dependent inhibition of insulin production. Therefore, we have identified a humoral connexion between the fat body and the brain insulin-producing cells relying on TNF-α that mediates adaptive response to nutrient deprivation.

Manon Lescaut : a lyric drama in four acts

Oletettavasti sama levytys kuin CD-julkaisussa RCA Victor Gold Seal Opera Series, 60573-2-RG, jossa tosin Plinio Clabassin tilalle merkitty Enrico Campi.

Beyond the obvious : three acts in educational drama

Researching research is not a common theme in educational drama. Nor is the educational drama process from a participant perspective a typical focus of research, at least not if the participants are disabled. Yet this is the theme of this thesis, a drama in three acts. The aim of this thesis is to describe, analyse, and discuss both the ways in which research within educational drama can be carried out and represented, and the experiences of the participants of the educational drama process. The theoretical framework that steers the research process is built up of two pairs of frames, each of them, like Russian nesting dolls, containing further frames. The first frame, relating to the outcomes of conducting research in educational drama, comprises philosophical, representational, and personal theories. As the second question asks what educational drama is, the subject related frame is built up of pedagogical, drama educational, and aesthetic theories. The study in its entirety follows the structure of the researcher’s hermeneutical learning process and takes the form of a journey starting from what is familiar, stretching towards what is new and different, and finally returning back to the beginning with a new view on what was there at the start. The thesis consists of two separate but related studies. The first, a familiar study conducted earlier, Alpha in Act I, was carried out among upper secondary school pupils. In the second, the new and therefore unfamiliar study, Omega in Act III, the participants are adult individuals who are physically and communicatively disabled. In between these two Acts an element of “Verfremdung” where the Alpha study is systematically scrutinized as the purpose is to teach and to manage the reader to think. Meta-discussions on the philosophical issues of the study are conducted throughout the text, parallel to the empirical parts. The outcomes of the first research question show that philosophical, methodical, and representational consistency is crucial for research. While this may sound like stating the obvious, this has nevertheless not always been considered fact, especially not within qualitative research. The outcomes further stress that representational issues are also to be recognized when presenting non-rational aspects of educational drama. By wording the world, through the use of visualising language, the surplus of meanings of educational drama can be, as they are within this study, made visible, sensible, and almost tangible, not only cognitively understandable. The outcomes of the second question point to the different foci of the studies, with Alpha focusing on the rationally retold experiences and Omega focusing on nonrational experiences. The outcomes expose educational drama as a learning process comprising doing, reflecting, and being. The doing aspect communicates the concrete efforts in creating a piece of theatre, while the being aspect relates experiences of being as situated, embodied and sensuous, reciprocal, empowering, aesthetic and artistic, and existential. Reflection is the twine that runs throughout the process and connects both doing and being. In summary, the outcomes could be formulated as “learning from learning how to make theatre”.

Soldiering and the making of Finnish manhood : conscription and masculinity in interwar Finland, 1918–1939

Military conscription and peacetime military service were the subjects of heated political, social and cultural controversies during the early years of national independence in Finland. Both the critics and the supporters of the existing military system described it as strongly formative of young men’s physical and moral development into adult men and male citizens. The conflicts over conscription prompted the contemporaries to express their notions about what Finnish men were like, at their best and at their worst, and what should and could be done about it. This thesis studies military conscription as an arena for the “making of manhood” in peacetime Finnish society, 1918–1939. It examines a range of public images of conscripted soldiering, asking how soldiering was depicted and given gendered meanings in parliamentary debates, war hero myths, texts concerned with the military and civic education of conscripts, as well as in works of fiction and reminiscences about military training as a personal experience. Studying conscription with a focus on masculinity, the thesis explores the different cultural images of manliness, soldiering and male citizenship on offer in Finnish society. It investigates how political parties, officers, educators, journalists, writers and “ordinary” conscripts used and developed, embraced or rejected these notions, according to their political purposes or personal needs. The period between the two world wars can be described as a fast-forward into military modernity in Finland. In the process, European middle class gender ideologies clashed with Finnish agrarian masculinities. Nationalistic agendas for the militarisation of Finnish manhood stumbled against intense class conflicts and ideological resistance. Military propaganda used images of military heroism, civic virtue and individual success to persuade the conscripts into ways of thinking and acting that were shaped by bourgeois mentality, nationalistic ideology and religious morality. These images are further analysed as expressive of the personal experiences and emotions of their middle-aged, male authors. The efforts of these military educators were, however, actively resisted on many fronts, ranging from rural working class masculinities among the conscripted young men to ideological critiques of the standing army system in parliament. In narratives about military training, masculinity was depicted as both strengthened and contradicted by the harsh and even brutal practices of interwar Finnish military training. The study represents a combination of new military history and the historical study of men and masculinities. It approaches masculinity as a contested and highly political form of social and cultural knowledge that is actively and selectively used by historic actors. Instead of trying to identify a dominant or “hegemonic” form of masculinity within a pre-determined theoretical structure, this study examines how the meanings ascribed to manhood varied according to class, age, political ideology and social situation. The interwar period in Finland can be understood as a period of contest between different notions of militarised masculinity, yet to judge by the materials studied, there was no clear winning party in that contest. A gradual movement from an atmosphere of conflict surrounding conscription towards political and cultural compromises can be discerned, yet this convergence was incomplete and many division lines remained.

The 42-kDa coat protein of Andean potato mottle virus acts as a transcriptional activator in yeast

Interactions of viral proteins play an important role in the virus life cycle, especially in capsid assembly. Andean potato mottle comovirus (APMoV) is a plant RNA virus with a virion formed by two coat proteins (CP42 and CP22). Both APMoV coat protein open reading frames were cloned into pGBT9 and pGAD10, two-hybrid system vectors. HF7c yeast cells transformed with the p9CP42 construct grew on yeast dropout selection media lacking tryptophan and histidine. Clones also exhibited ß-galactosidase activity in both qualitative and quantitative assays. These results suggest that CP42 protein contains an amino acid motif able to activate transcription of His3 and lacZ reporter genes in Saccharomyces cerevisiae. Several deletions of the CP42 gene were cloned into the pGBT9 vector to locate the region involved in this activation. CP42 constructions lacking 12 residues from the C-terminal region and another one with 267 residues deleted from the N-terminus are still able to activate transcription of reporter genes. However, transcription activation was not observed with construction p9CP42deltaC57, which does not contain the last 57 amino acid residues. These results demonstrate that a transcription activation domain is present at the C-terminus of CP42 between residues 267 and 374.

The calcium-dependent protease of Loxosceles gaucho venom acts preferentially upon red cell band 3 transmembrane protein

Eighty micrograms red blood cell (RBC) ghosts from patients who had previously exhibited the cutaneous form of loxoscelism (presenting localized dermonecrosis) and the viscerocutaneous form of loxoscelism (presenting dermonecrosis, hemoglobinuria, hematuria, and jaundice) and from controls were incubated with 2.5 µg crude Loxosceles gaucho venom in 5 mM phosphate buffer, pH 7.4, at 37ºC. Among all membrane proteins, quantitative proteolysis of the important integral transmembrane protein 3 increased with venom dose and with incubation time from 30 to 120 min, as demonstrated by gel densitometry. Similar quantitative data were obtained for RBC ghosts from patients and from control subjects, a fact that argues against the possibility of genetic factors favoring the hemolytic viscerocutaneous form. These data suggest that the clinical forms may be different types of the same disease, with the viscerocutaneous form being the result of large amounts of intravascularly injected venom and the superficial form being the result of in situ venom action. Since protein 3 is a housekeeping integral membrane protein, whose genetic deficiency leads to hemolytic anemia, it is reasonable to relate it to the hemolysis which occurs in the viscerocutaneous form of loxoscelism. The venom protease responsible for the process was not inhibited after 120-min incubation by 0.2 mM paramethylsulfonyl fluoride or by 0.2 mM N-ethylmaleimide but was inhibited by 25 mM ethylenediaminetetraacetic acid (a calcium-chelating agent) in 5 mM phosphate buffer at pH 7.4, which suggests that the enzyme is a calcium-dependent metalloprotease.